Protamines are simple proteins of low molecular weight that are rich in arginine and strongly basic. Protamines are extracted from the sperm of salmon and other fish species.
Protamine sulfate occurs as a fine white, or off white, amorphous or crystalline powder. It is sparingly soluble in water. The pH of protamine sulfate in solution is between 6.0 and 7.0. It is used to bind with heparin in the body. The cationic protamine at a pH of 6.8 to 7.1 reacts with anionic heparin at a pH of 5.0 to 7.5 to form an inactive complex.
Protamine sulfate may be supplied as a sterile, isotonic solution for administration to patients. It acts as a heparin antagonist and is also a weak anticoagulant.
When supplied as a pharmaceutical active ingredient, protamine sulfate contains four major peptides and other related peptides (or possible impurities). Presently, there are no reference standards available (including impurity standards). In addition, protamine sulfate may contain impurities in the form of nucleotides that in turn may derive from DNA present in the sample.
It is necessary to characterize protamine sulfate in order to satisfy various regulatory requirements before use in humans and other animals. Presently, there are no reference standards of the four major peptides comprising protamine sulfate or of related peptides or possible impurities. Thus, there remains in the art a need for improved methods for the analytical characterization of protamine sulfate.